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Biomedical subjects

S Paul

Publications and source records attributed to S Paul.

At least 19 recordsLinked to original sources

Identity of a membrane-bound vasoactive intestinal peptide-binding protein with calmodulin.

A vasoactive intestinal peptide (VIP)-binding protein purified from guinea pig lung membranes (p18) was digested with trypsin, and the amino acid sequence of the peptide fragments was determined. The sequence of six tryptic fragments of p18 was identical with subsequences present in mammalian calmodulin. Authentic porcine brain calmodulin and p18 co-migrated on an sodium dodecyl sulfate-electrophoresis gel and displayed identical chromatographic behavior on a reverse phase high performance liquid chromatography column. The VIP-binding properties of p18 and calmodulin were indistinguishable. Both proteins displayed saturable and apparent high affinity binding of VIP, evidenced by potent inhibition of complexation with [Tyr10-125I]VIP by unlabeled VIP (IC50 = 6.0-8.1 nM). Rat growth hormone releasing factor and a C terminally extended form of VIP ([Leu17]VIP-GKR) also displayed potent inhibition of the binding (IC50 = 6.4 and 4 nM, respectively). These neuropeptides are potential modulators of calmodulin function.

Amino Acid Sequence

Peptidolytic monoclonal antibody elicited by a neuropeptide.

We report evidence that a monoclonal antibody raised by immunization with a vasoactive intestinal peptide (VIP)-carrier protein conjugate selectively hydrolyzes VIP and a fluorescence quenched decapeptide (FQ14-22D), representing the region of VIP most susceptible to autoantibody-mediated cleavage (residues 14-22). A high affinity of the antibody for VIP and a lower affinity for FQ14-22D were revealed by kinetic studies and further substantiated by potent inhibition of FQ14-22D cleaving activity by full-length VIP. Sequencing of FQ14-22D hydrolysis products indicated selective cleavage at one peptide bond. These observations suggest that antibodies induced against naturally occurring polypeptide antigens can express peptidolytic activity targeted for specific sequences in the recognition epitope.

Amino Acid Sequence

Diarrheal disease in Cambodian children at a camp in Thailand.

The etiology of acute diarrhea (less than or equal to 3 days duration) and persistent diarrhea (greater than or equal to 14 days duration) was determined in Cambodian children under age 5 years in a refugee camp on the Thai-Cambodian border between May and October 1989; potential risk factors associated with persistent diarrhea were examined in an age-matched case-control study. Specimens collected from children and environmental sources were examined by standard microbiologic methods; Escherichia coli isolates were examined for hybridization with specific DNA probes and in tissue culture adherence assays. The same bacterial, viral, or parasitic agents were identified in 79 children with persistent diarrhea and in 408 children with acute diarrhea. Only one of nine children with persistent diarrhea excreted the same organism, Cryptosporidium, for that extended period. The most important risk factors identified for developing persistent diarrhea were living with other young children (odds ratio (OR) = 2.0, 95% confidence interval (Cl) 1.2-3.4) and being undernourished (OR = 2.6, 95% Cl 1.2-5.7). Persistent diarrhea in children in this camp was associated with several different agents rather than persistent infections with a single organism.

Cambodia

Role of cyclic AMP in adenosine inhibition of intracellular calcium rise in human platelets. Comparison of adenosine effects on thrombin- and epinephrine-induced platelet stimulation.

Thrombin-induced platelet aggregation is associated with an increase in intracellular calcium. Epinephrine provokes aggregation in the absence of a rise in intracellular calcium. Adenosine has been postulated as an endogenous inhibitor of platelet aggregation. In this study, the authors examine the effect of adenosine on the rise in intracellular calcium and on platelet aggregation, and the role of cyclic AMP (cAMP) in these actions. Human platelets were obtained from citrated plasma containing 5 micrograms/mL of indomethacin. Intracellular calcium was determined by fura-2 fluorescent dye. Adenosine inhibited thrombin-induced platelet aggregation and the rise in intracellular calcium in a dose-dependent manner. At a concentration of 100 mumol/L, adenosine completely inhibited thrombin-induced aggregation, but only partly inhibited the rise in intracellular calcium (55%). Adenosine also partially inhibited the rise in calcium produced by thrombin in both calcium-containing and calcium-free media, suggesting that adenosine inhibits both calcium influx and calcium mobilization. The effects of adenosine on intracellular calcium, as in the case of platelet aggregation, appear to be linked to adenylate cyclase, since they were prevented by the adenylate cyclase inhibitor 2',5'-dideoxyadenosine (1-mmol/L) and were potentiated by phospho-diesterase inhibition with papaverine (1 mumol/L). Adenosine and dibutyryl-cAMP also inhibited epinephrine-stimulated platelet aggregation in a dose-dependent manner. Thus, it appears that adenosine may inhibit platelet aggregation independently of its ability to decrease cytosolic free calcium.

Adenosine

Presence of exposed phospholipids in the outer membrane of Vibrio cholerae.

Vibrio cholerae 569B was found to be highly sensitive to a wide range of chemicals, particularly hydrophobic compounds and neutral and anionic detergents. The phospholipid profile of the outer membrane was similar to that reported for other Gram-negative bacteria. The lipopolysaccharide (LPS) contained O-antigenic sugars and exhibited heterogeneity. In addition, the LPS moiety was characterized by a relatively low negative charge. Analysis by topological probes revealed the presence of a significant amount of exposed phospholipids in the outer membrane. The reduced negative charge of LPS molecules and the exposed phospholipids present in the outer membrane could be important in the increased permeation of exogenous compounds in V. cholerae.

Binding Sites

Effect of hypothyroidism on different forms of actin in rat cerebral neuronal cultures studied by an improved DNase I inhibition assay.

An improved DNase I inhibition assay for the filamentous actin (F-actin) and monomeric actin (G-actin) in brain cells has been developed. Unlike other methods, the cell lysis conditions and postlysis treatments, established by us, inhibited the temporal inactivation of actin in the cell lysate and maintained a stable F-actin/G-actin ratio for at least 4-5 h after lysis. The new procedure allowed separate quantitation of the noncytoskeletal F-actin in the Triton-soluble fraction (12,000 g, 10 min supernatant) that did not readily sediment with the Triton-insoluble cytoskeletal F-actin (12,000 g, 10 min pellet). We have applied this modified assay system to study the effect of hypothyroidism on different forms of actin using primary cultures of neurons derived from cerebra of neonatal normal and hypothyroid rats. Our results showed a 20% increase in the Triton-insoluble cytoskeletal F-actin in cultures from hypothyroid brain relative to normal controls. In the Triton-soluble fraction, containing the G-actin and the noncytoskeletal F-actin, cultures from hypothyroid brain showed a 15% increase in G-actin, whereas the F-actin remained unaltered. The 10% increase in total actin observed in this fraction from hypothyroid brain could be totally accounted for by the enhancement of G-actin. The mean F-actin/G-actin ratio in this fraction was about 30% higher in the cultures from normal brain compared to that of the hypothyroid system, which indicates that hypothyroidism tends to decrease the proportion of noncytoskeletal F-actin relative to G-actin.

Actins

Test-retest reliability study of the Pennsylvania Bi-Manual Worksample.

Test-retest reliability of a vocational assessment battery called the Pennsylvania Bi-Manual Worksample (PBWS) (Roberts, 1969) was examined in this study. The PBWS was administered to 30 adults with developmental disabilities at two different times, with an interval of 7 to 10 days between administrations. The subjects, who had mild to moderate degrees of mental retardation and ranged in age from 25 to 51 years, were chosen randomly from a group of 95 employees of a sheltered workshop for adults with developmental disabilities in western New York. When the scores from the two test administrations were compared to determine test-retest reliability, a high intraclass correlation value of .98 was found, which indicates that the PBWS provides consistent information about the vocational skills of adults with developmental disabilities.

Adolescent

Cocaine abuse: an expanding healthcare problem for the 1990s.

Cocaine, the most addictive recreational drug available, has increased in popularity and widespread use in the past decade. Crack, a new form of cocaine that is smoked, is purer and more rapidly absorbed into the vascular system, greatly increasing the risk of overdose. Cocaine produces many physiologic effects on the body systems. This case report focuses on two cardiovascular responses related to cocaine use: cardiomyopathy and coronary vasospasm. Cocaine abusers may present with complaints of chest pain or other nonspecific symptoms that require diligent assessment skills to be recognized as cocaine-related. Therefore, it is essential that nurses be knowledgeable about the effects of cocaine and the symptoms of cocaine abuse.

Adult

Evaluation of the common cockroach Periplaneta americana (L.) as carrier of medically important bacteria.

The bacterial flora associated with external body parts, stomach and intestine of male and female Periplaneta americana inhabitating students' halls, teachers' residences and houses of low-paid employees in Jahangirnagar, University Campus were examined and analysed qualitatively and quantitatively. The qualitative study in P. americana revealed the presence of 31 species of bacteria belonging to 16 genera. Most of these bacteria are pathogenic to man and domestic animals. The total viable bacterial counts (TVBC/g) in students' halls, teachers' residences and houses of low-paid employees were 1.27 x 10(8), 6.04 x 10(7) and 1.65 x 10(8) respectively in the male and 1.43 x 10(8), 5.83 x 10(7) and 1.63 x 10(8) respectively in the female cockroaches. The highest prevalence of bacterial flora both in number and types occurred in stomach followed by intestine and the external body parts.

Animals

Dysphoric distress in childbearing women.

Previous research on depression in childbearing women has focused on the presence or absence of clinical depression. Little attention has been paid to the distress caused by the presence of depressive symptoms in the absence of the full syndrome of clinical depression. A convenience sample of 202 healthy, married, primigravid women who were free of psychiatric symptoms were assessed at 10 to 14 weeks and 30 to 32 weeks of pregnancy and at 1 to 2 weeks and 14 weeks post partum. Depression symptoms were measured by using the Schedule of Affective Disorders and Schizophrenia, the standardized clinical interview for research and depression of The National Institute of Mental Health. Data from the Schedule of Affective Disorders and Schizophrenia indicated that only 5% of the women met criteria for clinical depression but approximately 50% of the sample reported clinical levels of three or more depressive symptoms. Anger, fatigue, psychic anxiety, and worry were the most frequently endorsed symptoms at each assessment point. The implications of these findings for symptom management and health promotion for childbearing women are discussed.

Adult

Potential predictors of information-seeking behavior by homosexual/bisexual (gay) men with a human immunodeficiency virus seropositive health status.

Seeking ways to improve their health, gay men with human immunodeficiency virus (HIV) infections living in San Francisco are developing information networks and patterns of self-care behavior. Drawing from a set of explanatory theories, this cross-sectional survey with retrospective elements examined patterns and potential predictors of information-seeking activity in a cohort or 162 HIV seropositive (HIV+) men, 60 of whom provided complete data sets. The study suggests that 1 year after becoming aware of an HIV+ health status, most patients have developed multifaceted information networks. The amount of tangible aid acquired from these networks and frequency of consultation is positively related to patterns of HIV self-care behaviors and "feeling calm" (p less than 0.01), suggesting that these variables may be important markers for the need of supportive-educative nursing care. Suggestions for nursing practice and research are also described.

Bisexuality

Why bother the New Jersey State Department of Health?

The reporting of communicable diseases is a legal and professional responsibility. Individual case reports can be an important piece in a medical puzzle, allowing public health officials to describe new diseases and modes of transmission so preventive measures can be developed and implemented.

Communicable Disease Control

A phase I study of an outpatient regimen of recombinant human interleukin-2 and alpha-2a-interferon in patients with solid tumors.

This study was undertaken to define the maximum tolerated dose (MTD) of recombinant interleukin-2 (IL-2) that could be combined with a fixed dose of alpha-2a-interferon (alpha-IFN) in an outpatient setting. The schedule called for IL-2 to be given by a 2-hour intravenous infusion 5 days a week for 4 weeks. The alpha-IFN was given at a dose of 6 x 10(6) U/m2/d intramuscularly 3 days per week (Monday, Wednesday, and Friday). The IL-2 dose was escalated in four dose levels from 1 to 4 x 10(6) U/m2/d. The MTD in this study of 17 patients was at the fourth dose level of IL-2 (4 x 10(6) U/m2/d). In addition to the usual IL-2 toxicities, debilitating fatigue limited outpatient administration of this dose. Although the response rate was low, with partial responses seen in only 1 of 15 patients, 2 of 5 patients with melanoma treated at the higher dose levels had objective tumor shrinkage with one partial and one minor response. Thus, an IL-2 dose of 3 x 10(6) U/m2/d combined with a recombinant alpha-2a-IFN dose of 6 x 10(6) U/m2/d is recommended for Phase II studies.

Adult

Isolation of a low molecular mass vasoactive intestinal peptide binding protein.

A vasoactive intestinal peptide (VIP) binding protein was purified in active form by detergent solubilization of lung membranes, gel filtration, VIP-Sepharose affinity chromatography, reverse phase high performance liquid chromatography, and anion exchange chromatography. The mass of this protein was estimated at 18 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 17 kDa by gel filtration. The binding of VIP by this protein was inhibited by Mg2+, covalent cross-linking of [Tyr10-125I]VIP to the protein produced two radioactive bands at 22 and 26 kDa identified by electrophoresis, and the purified protein exhibited saturable and high affinity binding of VIP and the related neuropeptide, rat growth hormone releasing factor.

Animals

Cleavage of vasoactive intestinal peptide at multiple sites by autoantibodies.

Vasoactive intestinal peptide (VIP) fragments generated by autoantibodies purified from the blood of two human beings were separated and sequenced. Based on the identity of these fragments, seven peptide bonds cleaved by the antibodies were identified. Six of the seven scissile bonds are clustered in the region of VIP spanning residues 14-22 and were cleaved by antibodies from both human subjects. The seventh scissile bond is located at residues 7-8 and was cleaved by antibodies from one of the subjects. The scissile bonds link amino acid residues with different size, charge, and hydrophobicity. The hydrolytic activity of the antibodies was selective in that they failed to hydrolyze polypeptides unrelated in sequence to VIP (insulin and atrial natriuretic peptide). These observations demonstrate substrate specific hydrolysis by naturally occurring antibodies and expand the range of peptide bonds hydrolyzed by these antibodies.

Amino Acid Sequence

Vasoactive intestinal peptide hydrolysis by antibody light chains.

This paper describes evidence for hydrolysis of a neuropeptide, vasoactive intestinal peptide (VIP), by light chains purified from the IgG of a human subject positive for VIP binding antibodies. Purified IgG was digested with papain, resultant fragment antigen binding (Fab) fragments were reduced with 2-mercaptoethanol and alkylated with iodoacetamide, and light chains were purified by chromatography on immobilized antibodies to light chains and immobilized antibodies to heavy chains. Non-immunoglobulin components were undetectable in the light chain preparation, judged by sodium dodecyl sulfate-electrophoresis and Western blotting with anti-heavy and anti-light chain antibodies. The light chains hydrolyzed VIP with specific activity 32-fold greater than that of Fab, the pH optimum for light chain-mediated VIP hydrolysis was 7.0-7.5, and the hydrolytic activity was saturable (Vmax, 0.19 pmol/min/microgram light chains; substrate concentration at Vmax/2,380 nM).

Autoradiography

Demonstration that CFTR is a chloride channel by alteration of its anion selectivity.

Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) generates adenosine 3',5'-monophosphate (cAMP)-regulated chloride channels, indicating that CFTR is either a chloride channel or a chloride channel regulator. To distinguish between these possibilities, basic amino acids in the putative transmembrane domains were mutated. The sequence of anion selectivity of cAMP-regulated channels in cells containing either endogenous or recombinant CFTR was bromide greater than chloride greater than iodide greater than fluoride. Mutation of the lysines at positions 95 or 335 to acidic amino acids converted the selectivity sequence to iodide greater than bromide greater than chloride greater than fluoride. These data indicate that CFTR is a cAMP-regulated chloride channel and that lysines 95 and 335 determine anion selectivity.

Amino Acid Sequence